Hydroxylamines nucleophilic substitution

Tetranitro derivative 90 (z-TACOT Section 12.10.15.5) treated with methanolic sodium methoxide at ambient temperature does not lead to simple product of nucleophilic substitution of a nitro group but provides compound 92. Its formation can be rationalized by introduction of the methoxy group into the 1-position, followed by scission of the remote triazole ring of 91 to give the final product. Compound 90 subjected to the vicarious nucleophilic substitution (VNS) conditions using either hydroxylamine or trimethylhydrazinium iodide gives a very insoluble red solid, which was identified as l,3,7,9-tetraamino-2,4,8,10-tetranitrobenzotriazolo[2,l- ]benzotriazole 93 (Scheme 5) <1998JOC3352>. 

Unlike the 3-position, the 5-position is very susceptible to nucleophilic substitutions and additions. Thus, a series of publications report that 5-fluoroalkyl-l,2,4-oxadiazoles 94 undergo reaction with hydrazine or hydroxylamine to furnish 3-fluoroalkyl-l,2,4-triazoles 95 (X = NH) and 3-fluoroalkyl-1,2,4-oxadiazoles 95 (X = 0), a reaction that proceeds via addition of the nitrogen nucleophile to the 5-position (Scheme 9) <2005JOC3288, 2004EJ0974, 2003JOC605>. 

Electron-poor fused heterocyclic systems can activate a neighboring benzene ring for nucleophilic substitution. Fluoroquinolines of type 30 were shown to react efficiently with hydroxylamine (equation 20) . 

Nucleophilic substitution with heteroaryl halides is a particularly useful and important reaction. Due to higher reactivity of heteroaryl halides (e.g. 35, equation 24) in nucleophilic substitution these reactions are widely employed for synthesis of Al-heteroaryl hydroxylamines such as 36. Nucleophilic substitution of halogen or sulfonate functions has been performed at positions 2 and 4 of pyridine , quinoline, pyrimidine , pyridazine, pyrazine, purine and 1,3,5-triazine systems. In highly activated positions nucleophilic substitutions of other than halogen functional groups such as amino or methoxy are also common. 

No nucleophilic substitution in five membered heterocycles with hydroxylamines has been reported so far, although any nucleophilic substitution reaction known for amines should be suitable for hydroxylamines as well. 

Ho and coworkers" have observed that the addition of small amounts of solid KCN (0.2 equivalents) can effectively accelerate the formation of hydroxamic acids 112 from methyl esters 111 (Scheme 58). The authors suggested that this reaction proceeds through an acylcyanide intermediate followed by nucleophilic substitution by 50% aqueous hydroxylamine at room temperature. The use and advantage of this methodology have been demonstrated for both solution-phase and solid-phase applications. 

In contrast to the installation of the nucleobase via nucleophilic substitution of a suitable leaving group on the isoxazolidinyl cycloadduct, Colacino et al. (51) and Sindona and co-workers (52,53) prepared isoxazolidinyl nucleosides using vinyl nucleobases as the dipolarophile (Scheme 1.5). In Sindona s work, while a three-component reaction of hydroxylamine, formaldehyde, and 20 afforded a complex mixture of cycloadducts and byproducts, the known dipole 21 reacted with N-9-vinyladenine (20) in benzene at reflux to afford a racemic mixture of adduct 22 and its enantiomer (45%). The ester function was then used to effect a resolution by pig... 

As described previously <1996CHEC-II(4)743>, nucleophilic substitution in the benzene ring of 2, l, 3-bcnzosclc-nadiazole is known. Amination of 4-nitrobenzo-2,l,3-selenadiazole 143 with hydroxylamine and potassium hydroxide gave nitroamine 144 in 79% yield (Equation 8) <2004JHC955>. 

In his last years, Dr. Isbell became convinced of the importance of saccharide peroxides as reaction products, and not merely as intermediates. He pointed to the structural similarity that exists between hydrazines, hydroxylamines, and peroxides and suggested that a missing group, saccharide peroxides, might be prepared by nucleophilic substitution using suitably protected glycosyl halides and aryl peroxides, as shown in the scheme below. 

The reactions of tropone with hydroxylamine or hydrazine yield 2-aminotropone (59MI1, p. 415), in the first case admixed with troponeoxime (Section IV,A,8,b). Besides nucleophilic substitution, an additive mechanism was discussed (66MI2, p. 135 73CRV293, p. 354). 

Reaction of nitrosyl disulphonate, 0N(S03), with hydroxylamine-N-sulphonate is reported to be subject to catalysis by ferric salts at low concentrations, and to depend on the alkalinity through the hydrolysis of the catalyst . In mildly alkaline solution (pH 6-11), the rates of decomposition of this sul-phonate have been shown to be consistent with the existence of two reaction paths, one forming NO and the other sulphite radicals . The processes are assumed to represent bimolecular nucleophilic substitution by water. 

Nucleophilic substitution. The interesting reaction formulated is carried out by dissolving 20 g. of 1-nitronaphthalene and about 6 equivalents of hydroxylamine hydrochloride in 1.2 1, of 95% ethanol in a flask heated in a bath at 50-60°, and lO, NO,... 

The reaction employed to synthesize hydroxylamine, which produces die inteimediate N(0HKS03)2, probably involves the attack of HSOj (acting as a Lewis base) on N02 (acting as a Lewis acid), although, because the formal oxidation state of the N atom changes from +3 in N02 to +1 in N(0HXS03)2, this can also be seen as a redox reaction. Whether one considers reactions such as these to be redox reactions or nucleophilic substitutions may depend on the context in which the reactions being discussed. It is easy to see that these reactions do not involve simple electron transfer, such as in 2 Cu (aq) — Cu (s) + Cu (aq). 

Unsaturated jS-diketones (e.g. 122 R = H) and hydroxylamine generally yield isoxazoles. However, the nitro derivative (122 R = N02) with hydroxylamine in acetonitrile or acetic acid at 50°C yields the chloroisoxazoloan-thranil 124 (X = 0) by nucleophilic substitution and cyclization of the initially formed isoxazoline 123 as outlined in Eq. (6).149... 

The benzoyl acid ester CD is an important intermediate in CD modification. Selecting the appropriate nucleophile (iodide, azide, thio-amyl acetate and hydroxylamine, alkyl amines) to attack the carbon atoms which connect with tosyl, can trigger nucleophilic substitution reaction. Then, series of functional CD sulfonate derivatives can be obtained. 

It is assumed that hydroxylamine condenses with chloral to give oxime, which then undergoes the nucleophilic substitution with aniline, and hydrolyzes to give oximino intermediate under basic conditions. In the presence of a strong acid, such as concentrated sulfuric acid, the oximino compound cyclizes via nucleophilic addition of aromatic ring to C=N double bond. An illustrative mechanism is provided below. 

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